safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical effects of amg 557 in adults with psoriasis

Conditions: Psoriasis

Summary: the purpose of this study is to study the safety, tolerability and immunogenicity of amg 557 following multiple subcutaneous dose administration in adults with moderate to severe psoriasis.


Eligibility criteria:
inclusion criteria: * subjects must sign an institutional review board (irb)-approved informed consent form (icf) before any study specific procedures. * diagnosis of moderate to severe plaque pso for at least 6 months prior to screening as defined by: * a minimum pasi score of ≥ 10 obtained at screening; * psoriasis involving ≥ 10% of the body surface area (bsa) at screening. * received at least 1 previous phototherapy or systemic pso therapy (but not within the 30 days before study drug administration), or has been a candidate to receive phototherapy or systemic pso therapy in the opinion of the pi. * stable treatment without topical or systemic steroids, topical or systemic retinoids, vitamin d analogues (dovenex), psoralen ultraviolet a (puva) therapy, ultraviolet a (uva) therapy or ultraviolet b (uvb) therapy, methotrexate, or cyclosporine for at least 60 days prior to ip administration. stable treatment of pso involving scalp, axillae, or groin with topical corticosteroids of moderate strength will be allowed. * agrees to wear clothing that protects from sun exposure for the duration of the study. * agrees to use sunscreen (spf of at least 30) on sun-exposed skin for the duration of the study. * male or female subjects between 18 and 55 years of age, inclusive at the time of screening. * body mass index (bmi) between 18 and 35 kg/m2, inclusive, at screening, unless considered by the pi and the amgen medical monitor to be at an appropriate value in the context of other measured safety parameters. * able and willing to complete entire study (including skin biopsies) according to study schedule. * additional criteria per protocol. exclusion criteria: * diagnosis of guttate, pustular, or other non plaque forms of pso. * evidence of skin conditions other than pso (eg, eczema) during the screening period that would interfere with evaluations of the effect of ip on pso. * previous receipt of any approved or investigational biologic agent for pso or other medical conditions. * received puva therapy, uva therapy or uvb therapy ≤ 30 days prior to ip administration. * treatment with any other systemic pso therapy or oral or parenteral corticosteroids ≤ 30 days prior to ip administration. * use of high potency topical steroids, topical vitamin a or d analog preparations, or anthralin ≤ 30 days prior to ip administration (note: stable doses \> 30 days of low or moderate strength topical steroids are permitted only on the scalp, axillae, and groin according to the package insert). * received topical cyclosporin or calcineurin inhibitors such as pimecrolimus (elidel) and tacrolimus (protopic) ≤ 30 days prior to ip administration. * received iv or oral calcineurin inhibitors such as tacrolimus (prograf) ≤ 30 days prior to ip administration. * significant concurrent medical conditions at the time of screening or prior to randomization, including: * uncontrolled hypertension (defined as screening systolic blood pressure measurement of greater than 140 mm hg or a screening diastolic blood pressure of greater than 90 mm hg) confirmed by 2 separate measurements during the screening visit; * unstable angina pectoris; * congestive heart failure; * steroid or oxygen dependent chronic obstructive pulmonary disease; * diagnosis of multiple sclerosis or any other demyelinating disease; * open cutaneous ulcers; * uncontrolled diabetes (hba1c \> 7%). * history of myocardial infarction. * subjects with two or more cardiovascular risk factors (defined as bmi \> 30, bp systolic \> 140 mm hg, diagnosis of diabetes, history of cardiovascular event). * evidence of significant renal insufficiency during the screening period, defined by a glomerular filtration rate \< 50 ml/min using the cockcroft and gault equation: 72 x serum creatinine (in mg/dl) / (140 - age) x body weight (in kg) x \[0.85 if female\] * evidence of any bacterial, viral, parasitic, or systemic fungal infections during the 30 days prior to study drug administration (eg, common cold, viral syndrome, flu like symptoms). * evidence of a recent (within 6 months of randomization) infection requiring in patient hospitalization or intravenous antibiotics. * positive test for hiv antibodies, hepatitis b surface antigen, or hepatitis c antibodies. * underlying condition that predisposes the subject to infections (eg, history of splenectomy; history of immunodeficiency). * evidence of past or active tuberculosis on chest x-ray performed during screening (or documented evidence on a chest x-ray performed within 6 months prior to planned dosing); known tuberculosis antecedents; known exposure (without adequate treatment) to a person with active tuberculosis; or positive protein purified derivative (ppd) mantoux skin or serum quantiferon test at screening (without documented history of treatment). a positive result is defined as either induration greater than or equal to 5 mm 48-72 hours after administration (mantoux) or a positive serum quantiferon test result. * history of malignancy. * evidence of liver disease (eg, serum alt and ast \> 1.5 x the upper limit of normal) during screening period. * donated blood (including blood products) or experienced loss of blood ≥ 500 ml within 2 months of screening. * additional criteria per protocol.

Keywords: safety adult psoriasis inflammation